On October 10, the Army Research Office (ARO) MURI award headed by Michael Jewett at Northwestern University was held in Austin, Texas, with collaborators Eric Anslyn (Chemistry), Andy Ellington (Molecular Biosciences), Charles Schroeder (University of Illinois Urbana Champaign(UIUC)), Jeff Moore (UIUC), Eric Gaucher (University of Georgia), and Rhiju Das (Stanford University). This diverse team is attempting to recast the ribosome not as a protein-making machine, but as a more generic polymer-making machine. Already, recombinant protein production by the ribosome has transformed the lives of millions of people through the synthesis of biopharmaceuticals, like insulin, and industrial enzymes, like subtilisin, that are used in laundry detergents. In nature, however, only limited sets of protein monomers are utilized, thereby resulting in limited sets of biopolymers (i.e., proteins). Here, the team seeks to expand nature’s repertoire of ribosomal monomers to yield new classes of enzymes, therapeutics, materials, and chemicals with diverse genetically encoded chemistry. To this end, they have developed new technologies for charging tRNAs with non-amino acid substrates using Flexizymes (ribozyme tRNA synthetases) and have engineered other aspects of the translation machinery, including Elongation Factor Tu and the ribosome itself, to be able to utilize these non-standard monomers to make decidedly non-protein polymers. Overall, the goal of the group is to develop a means of making sequence-defined, electronically active polymers for any of a variety of applications of commercial and defense importance.
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